Towards Generalizable Protein-ligand Co-folding with ACER (opens in new tab)

Predicting protein-ligand complex structures is a central challenge in drug discovery. While recent co-folding models such as AlphaFold-3 achieve accurate structure prediction, they fail to generalize to underexplored binding interfaces - systematically misplacing ligands, particularly for allosteric or structurally novel targets. To address this gap, we present ACER (A daptive Co-folding via pocket E xploration and pose R anking), a training-free framework that (a) enables co-folding models ...